title: Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe.
abstract: Controlled human malaria infection (CHMI) studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection.
  
  
  
  We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18). Six participants received 2,500 sporozoites intradermally (ID), six received 2,500 sporozoites intramuscularly (IM) and six received 25,000 sporozoites IM.
  
  
  
  Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test).
  
  
  
  2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants.
  
  
  
  ClinicalTrials.gov NCT01465048.
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, United Kingdom ; The Jenner Institute Laboratories, University of Oxford, Oxford, United Kingdom.
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Sheehy
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Spencer
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Douglas
authors.forename: B Kim Lee
authors.initials: BK
authors.lastname: Sim
authors.forename: Rhea J
authors.initials: RJ
authors.lastname: Longley
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Edwards
authors.forename: Ian D
authors.initials: ID
authors.lastname: Poulton
authors.forename: Domtila
authors.initials: D
authors.lastname: Kimani
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Williams
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Anagnostou
authors.forename: Rachel
authors.initials: R
authors.lastname: Roberts
authors.forename: Simon
authors.initials: S
authors.lastname: Kerridge
authors.forename: Merryn
authors.initials: M
authors.lastname: Voysey
authors.forename: Eric R
authors.initials: ER
authors.lastname: James
authors.forename: Peter F
authors.initials: PF
authors.lastname: Billingsley
authors.forename: Anusha
authors.initials: A
authors.lastname: Gunasekera
authors.forename: Alison M
authors.initials: AM
authors.lastname: Lawrie
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D015925:Cryopreservation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000517:prevention & control; D009339:Needles; D010865:Pilot Projects; D013594:Syringes